MOLECULAR-CLONING OF HUMAN CATHEPSIN-O, A NOVEL ENDOPROTEINASE AND HOMOLOG OF RABBIT-OC2

A 1670-bp cDNA coding for a novel human cysteine protease has been iso lated from a monocyte-derived macrophage cDNA library. This cDNA predi cts a 329-amino acid preprocathepsin with more than 50% identity to bo th human cathepsin S and cathepsin L and 94% identity to a rabbit cDNA , termed OC2, recently isolated from osteoclasts. Based on its high ho mology to OC2, we have named the human enzyme cathepsin O. Cathepsin O mRNA was identified as a single similar to 1.7 kb transcript in cultu res of 15-day-old monocyte-derived macrophages, but was not expressed in human monocytes or alveolar macrophages. When transfected into COS- 7 cells, cathepsin O displayed potent endoprotease activity against fi brinogen at acid pH. This novel endoprotease may play an important rol e in extracellular matrix degradation.